7-((substituted)amino)-8-((substituted)carbonyl)-methylamino)-1-oxaspiro(4,5)decanes as analgesic agents

Abstract

Substituted phenoxy-, 1-, and 2-naphthalenyloxy-, indenyl-, indolyl-, benzofuranyl-, and benzo[b]thiofuranylcarboxamides of 7,8-(substituted-diamino)-1-oxaspiro[4.5]decanes are useful as analgesic agents. A method of making the compounds, pharmaceutical compositions employing the compounds, and a method of alleviating pain in warm-blooded animals are also disclosed.

I claim: 
     
       1. A compound having the structure ##STR17## wherein n is an integer of from one to six; either of X or Y is oxygen and the other is --CH 2  --; R 1  is selected from ##STR18##  where R 4  and R 5  are independently hydrogen, fluorine, chlorine, bromine, nitro, trifluoromethyl, alkyl of from one to six carbon atoms, alkoxy of from one to six carbon atoms, or aryl; ##STR19##  where R 6  is hydrogen, fluorine, chlorine, alkyl of from one to six carbon atoms, or aryl; Z is --CH 2  --, --O--, --S--, or --NR 7  -- where R 7  is hydrogen, alkanoyl of from two to six carbon atoms, or alkyl of from one to six carbon atoms; ##STR20##  where R 8  and R 9  are independently hydrogen, fluorine, chlorine, bromine , alkyl of from one to six carbon atoms, or alkoxy of from one to four carbon atoms; or ##STR21##  where R 8  and R 9  are as defined above; R 2  is methyl and R 3  is hydrogen; alkyl of from one to six carbon atoms,; ##STR22## --CH 2  --CH═CH 2 , --CH 2  C.tbd.CH; ##STR23## where R 10   is alkyl of from one to four carbon atoms; or where R 2  and R 3  when taken together with the nitrogen atom to which they are attached, form a pyrrolidinyl, piperidinyl, or hexahydro-1H-azepinyl ring;    and the pharmaceutically acceptable acid addition salts thereof.   
     
     
       2. A compound as defined in claim 1 wherein n is one. 
     
     
       3. A compound as defined in claim 1 wherein R 2  and R 3  taken together with the nitrogen atom to which they are attached form a pyrrolidinyl ring. 
     
     
       4. A compound as defined in claim 1 wherein R 1  is ##STR24## where R 4  and R 5  are as defined therein. 
     
     
       5. A compound as defined by claim 1 wherein ##STR25## where R 6  and Z are as defined therein. 
     
     
       6. A compound as defined by claim 5 wherein Z is --CH 2  --. 
     
     
       7. A compound as defined by claim 5 wherein Z is oxygen. 
     
     
       8. A compound as defined by claim 5 wherein Z is sulfur. 
     
     
       9. A compound as defined by claim 5 wherein Z is --NR 7  -- where R 7  is as defined therein. 
     
     
       10. A compound as defined by claim 1 wherein R 1  is ##STR26## where R 8  and R 9  are as defined therein. 
     
     
       11. A compound as defined by claim 4 having the name N-methyl-N-[7-(methyl-2-propynylamino)-1-oxaspiro[4.5]dec-8-yl]phenoxyacetamide. 
     
     
       12. A compound as defined by claim 7 having the name N-[7-[(cyclopropylmethyl)methylamino]-1-oxaspiro[4.5]dec-8-yl]-N,2-dimethylbenzo[b]furan-3-acetamide. 
     
     
       13. A compound as defined by claim 9 having the name N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-1H-indole-3-acetamide. 
     
     
       14. A compound as defined by claim 4 having the name N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-2-(3-nitrophenoxy)acetamide. 
     
     
       15. A compound as defined by claim 4 having the name N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-2-(3-trifluoromethylphenoxy)acetamide. 
     
     
       16. A compound as defined by claim 7 having the name N-methyl-N-[7[(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-2-bemzo[b]furanacetamide. 
     
     
       17. A compound as defined by claim 7 having the name N-methyl-N-[7[(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-3-bemzo[b]furanacetamide. 
     
     
       18. A compound as defined by claim 7 having the name N-methyl-N-[7[(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-4-bemzo[b]furanacetamide. 
     
     
       19. A compound as defined by claim 6 having the name N-methyl-N-[7-(methyl-2-propenylamino)-1-oxaspiro[4.5]dec-8-yl]-1H-indene-3-acetamide. 
     
     
       20. A compound as defined by claim 4 having the name 2-(4-fluorophenoxy)-N-methyl-N-[7-[methyl-(2-phenylethyl)amino]-1-oxaspiro[4.5]dec-8-yl]acetamide. 
     
     
       21. A compound as defined by claim 4 having the name 2-(3,4-dichlorophenoxy)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]acetamide. 
     
     
       22. A compound as defined by claim 4 having the name 2-(2,6-dichlorophenoxy)-N-methyl-N-[7-(-1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]acetamide. 
     
     
       23. A compound as defined by claim 4 having the name 2-(3,5-dichlorophenoxy)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]acetamide. 
     
     
       24. A compound as defined by claim 6 having the name N-methyl-N-[7-(1-pyrrolodinyl)-1-oxaspiro[4.5]dec-8-yl]-3-indeneacetamide. 
     
     
       25. A compound as defined by claim 9 having the name N-[7-(dimethylamino)-1-oxaspiro-[4.5]dec-8-yl]-N-methyl-1H-indole-3-acetamide. 
     
     
       26. A compound as defined by claim 4 having the name 2-(4-fluorophenoxy)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]acetamide. 
     
     
       27. A compound as defined by claim 10 having the name N-methyl-2-(1-naphthalenyloxy)-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]acetamide. 
     
     
       28. A method of alleviating pain in a warm-blooded animal comprising administering to said animal in need of such treatment an analgesically effective amount of a compound as defined by claim 1 in combination with a pharmaceutically acceptable carrier. 
     
     
       29. A compound as defined by claim 10 having the name N-methyl-N-[7-[methyl[2-(2-thienyl)ethyl]amino]-1-oxaspiro[4.5]dec-8-yl]-2-(1-naphthalenyloxy)acetamide. 
     
     
       30. A pharmaceutical composition useful for treating pain in a warm-blooded animal comprising an analgesically effective amount of a compound as defined by claim 1 in combination with a pharmaceutically acceptable carrier.